FDA

Sephience OK’d for phenylketonuria

August 1, 2025

Brand name: Sephience

Generic name: sepiapterin

Manufacturer: PTC Therapeutics

Approval date: July 28, 2025

FDA approved Sephience (sepiapterin), a phenylalanine hydroxylase (PAH) activator, for the treatment of hyperphenylalaninemia (HPA) in adult and pediatric patients ≥1 month of age with sepiapterin-responsive phenylketonuria (PKU). Sephience is to be used in conjunction with a phenylalanine (Phe)-restricted diet.

According to the manufacturer, sepiapterin is a natural precursor of the enzymatic co-factor BH4, a critical co-factor for PAH.

Efficacy

Approval was based on results from the phase 3 APHENITY trial (NCT05099640), in which sepiapterin (compared with placebo) reduced mean blood Phe levels from baseline to weeks 5 and 6 by 64.2% (95% confidence interval [CI], -74.1, -54.4). Mean change in blood Phe from baseline to weeks 5 and 6 was -415.8 μmol/L with sepiapterin vs. -19.9 μmol/L with placebo (treatment difference, -395.9 μmol/L; 95% CI, -463.1, -328.7; P <0.0001).

Safety

The most common adverse reactions reported in the trial (≥2% and greater than placebo) were diarrhea, headache, abdominal pain, hypophenylalaninemia, feces discoloration, and oropharyngeal pain.

Sources:

Sephience (sepiapterin) [package insert]. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/219666s000lbl.pdf Revised July 2025. Accessed July 31, 2025.

PTC Therapeutics announces FDA approval of Sephience™ (sepiapterin) for the treatment of children and adults living with phenylketonuria (PKU). [News release]. 2025. https://ir.ptcbio.com/news-releases/news-release-details/ptc-therapeutics-announces-fda-approval-sephiencetm-sepiapterin